Clermont Université, ENSCCF, EA 987, LCHG, BP 10448, F-63000 Clermont-Ferrand, France.
Eur J Med Chem. 2011 Sep;46(9):4035-41. doi: 10.1016/j.ejmech.2011.05.076. Epub 2011 Jun 12.
Synthesis and biological evaluation of new derivatives of Morphine-6-Glucuronide (M6G) are described. M6G is an active metabolite of morphine which displays more analgesia than morphine with a superior side effect profile but with a less efficiently BBB penetration. These phenomena could be explained by the presence of the glucuronide moiety, which confers a higher hydrophilic character compare to morphine. In this context, we have prepared three analogues of M6G possessing a tetrazole, an oxadiazole, and a triazolopyrimidine moiety instead of the carboxylic acid function on position 5 of the sugar. These three analogues showed higher analgesic properties than morphine and M6G even by oral administration.
描述了新的吗啡-6-葡萄糖醛酸苷（M6G）衍生物的合成和生物学评价。M6G 是吗啡的一种活性代谢物，其显示出比吗啡更强的镇痛作用，副作用谱更好，但血脑屏障穿透效率较低。这些现象可以用葡萄糖醛酸基的存在来解释，与吗啡相比，葡萄糖醛酸基赋予更高的亲水性。在这种情况下，我们已经制备了三种 M6G 的类似物，它们在糖的 5 位上具有三唑、恶二唑和三唑嘧啶取代羧酸功能。这三种类似物表现出比吗啡和 M6G 更强的镇痛作用，甚至通过口服给药也是如此。
